Pheochromocytoma differential diagnosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ahmad Al Maradni, M.D. [2] Mohammed Abdelwahed M.D[3]

Overview

Pheochromocytoma must be differentiated from other causes of paroxysmal hypertension including severe paroxysmal hypertension (Pseudopheochromocytoma), panic disorder, Factitious hypertension, carcinoid syndrome, Migraine headache, Hyperthyroidism, Renovascular hypertension, Hypoglycemia, Labile hypertension (White coat hypertension), Stroke and compression of the lateral medulla, Seizures, Baroreflex failure and drugs.

Differentiating pheochromocytoma from other diseases

Pheochromocytoma must be differentiated from other causes of paroxysmal hypertension including severe paroxysmal hypertension (Pseudopheochromocytoma), panic disorder, Factitious hypertension, carcinoid syndrome, Migraine headache, Hyperthyroidism, Renovascular hypertension, Hypoglycemia and drugs.

Disease	Symptoms	Signs	Investigations
Pheochromocytoma	The hallmark symptoms of a pheochromocytoma are those of sympathetic nervous system hyperactivity, symptoms usually subside in less than one hour and they may include: Palpitations especially in epinephrine producing tumors.[3] Anxiety often resembling that of a panic attack Sweating Headaches occur in 90 % of patients. paroxysmal attacks of hypertension but some patients have normal blood pressure. May be asymptomatic and discovered by incidence screening especially MEN patients. Please note that not all patients with pheochromocytoma experience all classical symptoms.[4]	Common physical exam findings include: Tachycardia Hypertension, including paroxysmal (sporadic, episodic) high blood pressure, which sometimes can be more difficult to detect. Orthostatic hypotension	High-risk patients: plasma fractionated metanephrines are the first test if elevated; 24-hour urinary fractionated metanephrines, catecholamines, and imaging should be the second test for diagnosis. [2] Low-risk patients: 24-hour urinary fractionated catecholamines and metanephrines.[4]
Pseudopheochromocytoma	Paroxysmal activation of the sympathetic system causing hypertension and tachycardiathat responds to alpha/beta blockade.Disorder is usually related to emotional distress. Acute onset of high blood pressure, headache, chest pain, nausea, palpitations, flushing. Duration of attacks ranges from minutes to hours.		Increase in plasma catecholamines between and during attacks.
Panic attacks	Paroxysms of increased sympathetic activity. It is characterized by episodes of fear or panic Such as pseudo-pheochromocytoma, panic disorders are usually associated with physical symptoms such as chest pain, headache, palpitations, flushing and both respond to antidepressants.	In panic attacks, fear precedes physical symptoms. By contrast, in pseudo pheochromocytoma physical symptoms occur before feeling fear.	Laboratory studies that can exclude medical disorders other than panic disorder include: Serum electrolytes Serum glucose Cardiac enzymes Urine toxicology screening
Labile hypertension (White coat hypertension)	Patients exhibit elevated blood pressure in a clinical setting but not in other settings.[1]	Ambulatory blood pressure monitoring and patient self-measurement using a home blood pressure monitoring device are being increasingly used to differentiate patients with white coat hypertension from patients with true hypertension.	Normal laboratory studies
Hyperthyroidism	Symptoms of hyperthyroidism include weight loss, heat intolerance, tremor, palpitations, anxiety, increased bowel disturbances, and shortness of breath.	Goiter, skin flushing and eye proptosis. Increased sensitivity of beta receptors in the heart to catecholamines due to an effect of thyroid hormones increase cardiac work and output and systolic hypertension.	Low thyroid-stimulating hormone (TSH), high free thyroxine (T4), and triiodothyronine (T3) concentrations
Renovascular hypertension	Age of hypertension < 30 years and > 55 years Abrupt onset of hypertension Accelerated hypertension that was previously well-controlled Refractory hypertension to 3 anti-hypertensive medications Malignant hypertension	(bruit) can be heard over the abdomen.	Diagnosis by Duplex ultrasonography is considered class I recommendation. It may be used as an initial screening tool for diagnosis of atherosclerotic renal artery stenosis. Ultrasonography might not be very accurate in obese patients or those intestinal gas.[1]
Stroke and compression of lateral medulla (Lateral medullary syndrome)	Extensive unilateral infarction of the brain stem in the region of the nucleus tractus solitarius may result in partial baroreflex dysfunction, increased sympathetic activity, and neurogenic paroxysmal hypertension.		CT shows mass compressing lateral medulla or infarction in the same area.
Seizures	According to type; it may be focal or generalized, clinical or subclinical: A person having a tonic-clonic seizure may have repetitive twitches of arm and legs. Patients may have tongue pittings and may lose consciousness. Symptoms occur suddenly and may persist Muscle tension or tightening that causes twisting of the body, head, arms, or legs. Patients may have amnesia. Mood changes for example; fear, panic, or laughter Change in sensation of the skin over the arm, leg, or trunk Vision changes and light flashes and may be hallucinations Tasting a bitter or metallic flavor A person having a complex partial seizure may appear confused or dazed and will not be able to respond to questions or direction. absence seizure is a rapid blinking or a few seconds of staring into space.		An abnormal electroencephalography. Positive test without a clinical presentation is called sub clinical seizure. They may identify past or family history of epilepsy.
Carcinoid syndrome	Hypertensive crisis occurs with malignant carcinoid syndrome should be distinguished from pheochromocytoma.	Cutaneous flushing Venous telangiectasia, diarrhea, bronchospasm and cardiac valvular lesions (tricuspid incompetence)	High urinary excretion of 5-HIAA High urinary excretion of serotonin High chromogranin concentration. Chromogranin(designated as A, B, and C) are proteins that are stored and released with peptides and amines in a variety of neuroendocrine tissues. CT is recommended for evaluation of all patients with carcinoid tumors.
Migraine headaches	(1) Prodrome which occurs hours or days before a headache (2)  Aura which immediately precedes the headache (3) The pain phase, also known as headache phase (4) The postdrome phase	Conjunctival injection may be present. Horner's syndrome [1] may be present. Adie type pupil [2] may be present. Cranial/ cervical muscle tenderness may be present. Listen for bruit at neck and head for clinical sights of an arteriovenous malformation.	CT is indicated in patients with[1] [2] Abnormal physical examination Increase of headache's frequency Poor coordination Focal neurologic signs Headache's awakening the patient at night[3][4] Atypical aura: sudden onset, lasting more than 1 hour, always at the same side and/or without visual symptoms Migraine attacks that begin after 50 years of age CT is not indicated in: Patients with a diagnosis of a migraine in accordance with the criteria for migraine Differentiating a migraine from other primary headaches
Drugs	Sympathomimetic drugs that can induce symptoms simulating pheochromocytoma include high-dose phenylpropanolamine, cocaine, amphetamine, LSD, PCP.  Combination of a monoamine oxidase (MAO) inhibitor and ingestion of tyramine-containing foods.	Disturbed consciousness Nasal septum perforation in cocaine addiction Needle marks on the skin History of antidepressants intake	Toxicology screening
Baroreflex failure	Marked and frequent fluctuations in blood pressure, with both high and low readings It is caused by hypofunctioning of t-he baroreflexes that normally buffer blood pressure fluctuations. The disorder is usually a result of injury to carotid baroreceptors, with most patients reporting a history of neck irradiation or surgery.		Neck CT